Barbosa Raquel, Bastos Paulo, Pita Lobo Patrícia, Rodrigues Catarina Correia, Valadas Anabela, Correia Guedes Leonor, Mano Beatriz, Alberto Sara, Paixão Vitor, Rosa Mário Miguel, Matias Ricardo, Martins Daniel, Mendonça Marcelo, Coelho Miguel
Neurology Department, Centre Hospitalier Universitaire Toulouse, Toulouse, France.
Nova Medical School, Faculdade de Ciências Medicas, Universidade Nova de Lisboa, Lisbon, Portugal.
Mov Disord Clin Pract. 2025 Jun 12. doi: 10.1002/mdc3.70170.
The long-term efficacy of high-frequency subthalamic nucleus deep brain stimulation (STN-DBS) on freezing of gait (FOG) remains unclear. We aimed to study the mechanism and optimal therapeutic approach to long-term post-surgery FOG.
The aim was to assess the mechanism and optimal therapeutic approach to long-term post-surgery FOG.
Seventeen Parkinson's disease (PD) STN-DBS patients with a FOG score (item 3.11) ≥2 in the MedON/StimON condition were evaluated under 5 experimental conditions, including a low-frequency (60 Hz) condition maintaining the same total energy delivered. In each condition, gait and FOG episodes (#FOG) were assessed using clinical (eg, a 3 × 14-m Stand-Walk-Sit Test) and kinematic data from inertial measurement units (IMU).
Compared to MedOFF/StimOFF, #FOG significantly decreased in the MedON/StimON 130-Hz condition. Either stimulation or levodopa (LD) (MedOFF/StimON or MedON/StimOFF) also significantly reduced #FOG and Stand-Walk-Sit Test (SWS) time compared to MedOFF/StimOFF. No significant difference in #FOG episodes or SWS time was found between 130 and 60 Hz, though 60-Hz stimulation had lower axial scores. Individual responses to LD or stimulation varied: (1) 3 patients improved #FOG with LD but worsened with stimulation, whereas 5 exhibited the reverse; (2) in 9 patients, low-frequency stimulation outperformed high-frequency stimulation in reducing #FOG. Gait variability was the strongest kinematic dimension associated with FOG, with severity accurately identified via a neural network trained on sensor data.
Post-DBS FOG in the best-functional state is largely therapy resistant, partially improved by stimulation and medication. Individual variability in responses to LD and stimulation underscores the need to determine FOG circuit mechanisms, as treatment remains an unmet clinical need.
高频丘脑底核深部脑刺激（STN-DBS）对步态冻结（FOG）的长期疗效尚不清楚。我们旨在研究术后长期FOG的机制及最佳治疗方法。
评估术后长期FOG的机制及最佳治疗方法。
对17例在MedON/StimON状态下FOG评分（项目3.11）≥2的帕金森病（PD）STN-DBS患者在5种实验条件下进行评估，包括维持相同总能量输出的低频（60Hz）条件。在每种条件下，使用临床方法（如3×14米站立-行走-坐立测试）和来自惯性测量单元（IMU）的运动学数据评估步态和FOG发作次数（#FOG）。
与MedOFF/StimOFF相比，在MedON/StimON 130Hz条件下#FOG显著减少。与MedOFF/StimOFF相比，刺激或左旋多巴（LD）（MedOFF/StimON或MedON/StimOFF）也显著减少了#FOG和站立-行走-坐立测试（SWS）时间。虽然60Hz刺激的轴向评分较低，但在130Hz和60Hz之间未发现#FOG发作次数或SWS时间有显著差异。个体对LD或刺激的反应各不相同：（1）3例患者LD改善了#FOG，但刺激使其恶化，而5例则相反；（2）9例患者中，低频刺激在减少#FOG方面优于高频刺激。步态变异性是与FOG相关的最强运动学维度，通过基于传感器数据训练的神经网络可准确识别其严重程度。
处于最佳功能状态的DBS术后FOG在很大程度上对治疗有抵抗性，刺激和药物可部分改善。个体对LD和刺激反应的变异性突出了确定FOG回路机制的必要性，因为治疗仍然是未满足的临床需求。
